This proposed research is intended to delineate the changes in the functional properties of heart muscle in chronic diabetes and the influence of therapeutic intervention. One phase of the work will focus upon the basis for increased stiffness of left ventricular muscle and accumulation of glycoproteins in the interstitium. The metabolism of cardiac muscle cells will be evaluated from the point of view of the synthesis of phospholipid and cholesterol in the cell membranes. The significance of morphologic abnormalities in the intramural vessels will be investigated by determining flow rates in response to various afterload increments. In addition, the basis for the exaggerated response of the diabetic heart to acute coronary vessel occlusion will be assessed to determine whether the altered cell metabolism or composition of interstitium in the nonischemic area is a determinant of the greater reduction of ventricular function in diabetics. In evaluating acute myocardial ischemia per se, we are determining the influence of cell acidosis on the change in ventricular function as well as the influence of reconstitution of blood flow with coronary bypass surgery and the possible sustained therapeutic effects to be achieved with appropriate use of catecholamines or infusion of a glucose substrate.